This study evaluated the association between depressive symptoms and health related quality of life (HRQoL) in patients with chronic pulmonary disease using both general and disease-specific HRQoL measures. A cross-sectional analysis of HRQoL measures completed by patients enrolled in the Department of Veteran Affairs Ambulatory Care Quality Improvement Project. 1252 patients with chronic pulmonary disease screened positive for emotional distress and returned the Hopkins Symptom Checklist-20 (SCL-20). 733 of 1252 had a score of 1.75 or greater on the SCL-20 indicating significant depressive symptoms. Depressive symptoms were associated with statistically significantly worse general and pulmonary health as reflected by lower scores on all sub-scales of both the Medical Outcomes Short Form-36 and the Seattle Obstructive Lung Disease Questionnaire. In fact, 11% to 18% of the variance in physical function sub-scales was attributed to depressive symptoms alone. Patients with chronic pulmonary disease and depressive symptoms reported significantly more impaired functioning and worse health status when compared to those patients without depressive symptoms. Because there are highly effective treatments for depression, selective screening of patients with chronic pulmonary disease for depression may identify a group that could potentially benefit from treatment interventions.